Project 5/Core A An advantage of conducting research within a coordinated Program Project is the ability to create core facilities to (i) efficienfiy and economically share resources and administrafion support, (ii) provide infrastructure for the scientific objectives of the program, (iii) provide mechanisms for disseminafing results and facilitafing discussions within the group, and (iv) coordinate interactions with outside investigators to obtain crifieal evaluation, technical advice and intellectual input to keep the work on track and at the cuing edge of technologies in the field. To this end an Analytical, Administrative and Animal Core (Core A) will be created and directed by Dr. Chrisfine Gall. Core A will address 6 specific aims. Aim 1 is to establish a facility within the Core, for Deconvolution Microscopy-Image analysis, Electrophysiology, Behavioral Assays and BDNF Protein Assays to provide for shared analytical needs ofthe various subprojects, to ensure that data obtained within the program can be reliably compared across projects, and to make most the economical use of resources and technical support; this will include training and oversight of technical personnel. Aim 2 is to oversee the purchase of animals, genotype mice for the entire program, and establish a video- monitored system for behavioral studies. In addition, the Core will manage the costs associated with maintaining breeding mouse colonies. Aim 3 is to provide ampakine drugs and neurotrophin reagents (BDNF peptides and antagonists) to subprojects; this includes contracting the synthesis of ampakines from outside sources. Aim 4 is to coordinate collaborations and integration of research results among subproject laboratories. This will be accomplished through monthly meetings of all program investigators in addition to more frequent meetings of smaller collaborative groups. Aim 5 is to coordinate interactions with outside investigators to provide review and oversight, technical advice, and outside intellectual input to program investigators. To this end, formal internal and external advisory board have been created; each is composed of outstanding investigators with specific expertise relating to objectives ofthe program Subprojects. Aim 6 is to provide general administrafive support and computer assistance for all program investigators, and to assure ongoing compliance with institufional regulafions pertaining to material use, animal research, and laboratory safety. RELEVANCE (See instructions): The program project will test if there are common neurobiological processes underlying cognitive impairments in different animal models and if up-regulating BDNF is a broadly effective therapeutic strategy. To meet these program goals is critical that the different subprojects use the same treatments and measures. The Core will assure this uniformity and will provide mechanisms for sharing critical analytical facilities, technical expertise, and research advances throughout the program.